The capability of the extracellular slime glycolipoprotein (GLP) of Pseudomonas aeruginosa to activate human complement was investigated. When slime GLP was added to type AB human serum, C3 and factor B were converted to their respective major cleavage fragments, C3b and Bb. This activation also occurred when slime GLP was incubated with serum-ethylene glycol bis(trichloroacetate)-Mg++, a result which indicates that the alternative complement pathway is involved. Additional support for the hypothesis of alternative pathway activation was provided by the fact that when serum-ethylene glycol bis(trichloroacetate)-Mg++ was preheated to inactivate factor B, slime GLP did not induce conversion of C3. The activation of the alternative pathway of human complement by slime GLP may represent an early nonimmune defense against P. aeruginosa infection.